Approximately 30 million Americans suffer from migraine headaches. Migraine is a potentially chronic, progressive disease that substantially affects patients, families, workplaces, and society. More than 20% of migraine headaches start before the age of 10 and 45% before the age of 20 and can appear in children as young as 4 years old. It has previously been considered an episodic disorder, but now is thought to be a progressive disease affecting the brain that negatively affects all aspects of an individual's life particularly during formative and productive years. Here we propose to use multimodal approaches brain imaging approaches to evaluate functional, morphometric (gray matter volume and white matter integrity) and chemical changes in the brains of cohorts of acute episodic migraineurs from 7 to 27 years of age. By approaching he problem using development (age), we propose to demonstrate: (1) that male and female migraineurs at different ages (prepubertal, pubertal, and young adult cohorts) have significantly different brain processing compared with controls; (2) that progression of brain changes may differentiate and provide novel insights into changes in the female brain during puberty/adolescence; and (3) that measures of migraine effects on the young brain (prepubertal) may provide insights into core brain changes involved in migraine independent of hormonal effects. We wish to test the hypotheses that there are age-related differences similarities in the migraine brain and that early changes may predict the long duration/course of the disease. We have the necessary expertise in imaging, migraine neurobiology and neurology, and preliminary data for each aspect of the proposed research. We expect to gain insights on how the migraine brain presents with ageing that may provide novel approaches to therapy particularly at a young age when the disease begins in a significant number of individuals. PUBLIC HEALTH RELEVANCE: Using functional imaging techniques, the proposed research will evaluate and compare the structure, chemistry and function of brains of patients with migraine who suffer from migraine at different ages. The data should provide evidence for how brains are changed in different age groups and how we use this approach to provide a basis for evaluation of medications to limit the progression of the disease.